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Interferon-b (IFN-b) is the major treatment for multiple sclerosis. However, this treatment is not always effective. Here we have found congruence in outcome between responses to IFN-b in experimental autoimmune encephalomyelitis (EAE) and relapsing-remitting multiple sclerosis (RRMS). IFN-b was effective in reducing EAE symptoms induced by T helper type 1 (TH1) cells but exacerbated disease induced by TH17 cells. Effective treatment in TH1-induced EAE correlated with increased interleukin-10 (IL-10) production by splenocytes. In TH17-induced disease, the amount of IL-10 was unaltered by treatment, although, unexpectedly, IFN-b treatment still reduced IL-17 production without benefit. Both inhibition of IL-17 and induction of IL-10 depended on IFN-g. In the absence of IFN-g signaling, IFN-b therapy was ineffective in EAE. In RRMS patients, IFN-b nonresponders had higher IL-17F concentrations in serum compared to responders. Nonresponders had worse disease with more steroid usage and more relapses than did responders. Hence, IFN-b is proinflammatory in TH17-induced EAE. Moreover, a high IL-17F concentration in the serum of people with RRMS is associated with nonresponsiveness to therapy with IFN-b.

Read More: T helper type 1 and 17 cells determine efficacy of interferon-b in multiple sclerosis and experimental encephalomyelitis